Toxicology Research最新文献

The current research aims to map the spatial distribution of potentially toxic elements (PTEs) (As, Co, Cr, Cu, Fe, Mn, Ni, V, and Zn) in Qena southern of Egypt, identify the sources of PTEs using geostatistical analysis (principal component analysis, cluster analysis, and correlation matrix(, and determine the level of contamination in the study area to assess soil contamination with selected potentially toxic elements. To accomplish this, thirty soil samples were gathered and examined for the PTEs. The variability of the soil chemical content was estimated using multivariate geostatistical analysis. All PTEs, with the exception of As, show a strong positive association with one another in the correlation matrix. Two components illustrated through the principal component analysis (PCA). The primary source of the first component, which accounts for the majority of the variance, is a combination of industrial activity and agricultural activities. It is rich in Co, Cr, Cu, Fe, Mn, Ni, V, and Zn. As is abundant in the second component, and lithology may be the source. According to the Pollution Load Index (PLI), 61% of the study area (west and south of the study area) was contaminated, and 31% of the study area (east of the study area) was unpolluted. The Degree of Contamination (DC) index was used to classify the research region as low, moderate, and considerably contaminated, with percentages of 21, 51, and 28% of the study area, respectively. The Nemerow Pollution Index (NPI) classifies the majority of samples (63.33%) as slightly to moderately polluted. The study's conclusions showed that to evaluate the potential risk to the environment, PTEs concentrations in the study area need to be monitored. This study aligns with key UN Sustainable Development Goals (SDGs), particularly SDG 3 (Good Health) and SDG 15 (Life on Land), by to safeguarding both human well-being and terrestrial ecosystem health. Moreover, the study provides a scientific basis for sustainable environmental management, supporting the transition towards safer and more resilient communities.

Indoxacarb (IND) is a toxic pesticide that can cause several organ damages in non-target organisms. However, to date no study has investigated the impacts of IND on hepatic tissues at various concentrations. Therefore, this investigation was executed to evaluate the dose-dependent effect of IND on hepatic tissue. Albino rats (Rattus norvegicus) (n = 36) were divided into four groups: control and three IND concentrations (30, 60, and 90 mg/kg). IND exposure showed a notable reduction in the gene expression of Estrogen-Related Receptor Alpha (ERRα), nuclear respiratory factor-1 (NRF-1), mitochondrial transcription factor-A (TFAM), peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α), nuclear respiratory factor-2 (Nrf-2), and silent information regulator sirtuin-1 (SIRT1) while increasing the expression of adenosine monophosphate-activated protein kinase (AMPK). Moreover, IND exposure decreased the activities of catalase (CAT), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione reductase (GSR) while increasing the levels of ROS and MDA. However, an increase was recorded in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) whereas the levels of albumin and total proteins were decreased after high dose (90 mg/kg) of IND. IND concentration (30, 60, and 90 mg/kg) induced apoptosis by increasing the levels of Bax, Caspase-9 and Caspase-3 while diminishing the levels of Bcl-2 and displayed adverse impacts on hepatic histological profile. In conclusion, the IND administration at all the tested doses cause severe hepatic damage via dysregulation of AMPK/SIRT1/NRF-2/ERRα, increasing oxidative stress, decreasing antioxidant defense, leading to inflammation, apoptosis and changes in the hepatic histology.

Methotrexate, used in the treatment of various cancers, induce oxidative stress, inflammatory response, apoptotic cell death and ultimately toxic lung damage when used for a long time or in excessive doses. Prevention of overproduction of reactive oxygen species and maintenance of cellular redox balance can be facilitated by the use of various natural antioxidants and essential oils. The aim of this study was to investigate the protective role of Alpha Pinene, a plant component known to have antioxidant, anti-inflammatory and cytoprotective properties, against Methotrexate-induced lung damage in rats. For this purpose, 35 adult male rats were randomly divided into 5 groups as Control, Vehicle, Methotrexate (20 mg/kg, single dose), Alpha Pinene (50 mg/kg/day) and Methotrexate+Alpha Pinene. At the end of the 14-day experimental period, the removed lungs were first weighed, then oxidative stress (superoxide dismutase, catalase and malondialdehyde) and apoptosis (APAF-1 and Caspase-3) parameters were measured, then the Heat Shock Protein 70 levels were determined, and finally Haematoxylin-Eosin and Masson's Trichrome stains were performed to evaluate histologic tissue damage. The data obtained revealed that Alpha Pinene significantly reduced Methotrexate induced changes in the oxidative stress and apoptosis parameters and Heat Shock Protein 70 levels. It was also shown to have a protective effect on the lungs against acute Methotrexate toxicity, preventing alveolar epithelial damage, congestion, inflammatory cell infiltration and alveolar degeneration despite the presence of mild fibrosis and interstitial edema. Alpha Pinene can be considered to be a highly valuable protective agent against Methotrexate-induced lung injury.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), one of the most prevalent chronic liver diseases worldwide, has a pathogenesis that remains incompletely understood. In recent years, Bisphenol A (BPA) has been recognized as an emerging pathogenic factor for MASLD as an environmental contaminant. By integrating multiple advanced methodologies including Network Toxicology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation, this study systematically elucidates the molecular mechanisms underlying BPA-induced MASLD. Through analysis of NHANES data, we identified a significantly positive correlation between BPA levels and MASLD risk. Integration of multiple databases identified 34 potential BPA-related targets. KEGG enrichment analysis revealed the critical role of the PI3K/AKT signaling pathway in MASLD, with COL1A1, COL1A2, and IGF1 serving as core targets that drive disease progression. Immune cell infiltration analysis demonstrated that BPA regulates immune cell function via the PI3K/AKT pathway, thereby promoting the onset and development of MASLD. These findings reveal the complex mechanisms underlying BPA-induced MASLD and provide novel therapeutic targets, along with theoretical support for the early screening and precision treatment of this disease.

Extensive clinical and epidemiological studies have shown that Aristolochic acids (AA) exhibit significant nephrotoxicity, mutagenicity, and carcinogenicity. This study aimed to systematically explore the potential molecular mechanisms by which AA induce urinary system tumors using a network toxicology approach.The carcinogenic potential of AA was predicted using ProTox, ADMETlab, and admetSAR. Potential targets of AA were identified via SEA, SwissTargetPrediction, and TargetNet, and then intersected with urinary tract tumor related genes obtained from the GeneCards database to yield common targets. A protein-protein interaction network was constructed, and GO and KEGG enrichment analyses were performed to determine their functional characteristics. LASSO regression models were built using TCGA datasets for prostate cancer, clear cell renal cell carcinoma, and bladder cancer to screen survival related hub genes. Finally, molecular docking of AA with the key targets was conducted using the CB-Dock2 platform. A total of 27 overlapping targets between AA and the three urinary tract tumors were identified. Enrichment analysis indicated that these targets are significantly involved in apoptosis, inflammatory responses, and cancer related pathways such as PI3K-Akt and MAPK. The LASSO regression models exhibited good prognostic performance across all three tumor types, with CASP3 identified as a common and significant core gene. Molecular docking analysis showed that AA can stably bind to the active pocket of CASP3.CASP3 may serve as a common key target in AA-induced urinary tract tumorigenesis. These findings provide novel theoretical insights into the molecular mechanisms by which AA promote the development of urinary system cancers.

Propofol is a widely used intravenous anesthetic for the induction and maintenance of general anesthesia. Although clinical observations have suggested potential nephrotoxic effects of propofol, experimental evidence remains limited. In this study, we investigated the renal effects of propofol in vitro using human renal proximal tubular epithelial (HK-2) cells. Our results demonstrate that propofol induces persistent oxidative stress and mitochondrial dysfunction, leading to apoptosis. Notably, propofol activates the JNK/c-JUN signaling pathway, which in turn promotes epithelial-to-mesenchymal transition (EMT), as evidenced by morphological changes and increased expression of mesenchymal markers such as vimentin and Snail. These findings suggest a mechanistic link between prolonged propofol exposure and renal fibrotic responses. Our work highlights the need for greater awareness of propofol-associated renal risks and provides a basis for future research into its underlying molecular mechanisms.

The liver and kidneys are central to maintaining systemic homeostasis by removing endogenous and exogenous toxins. However, toxin accumulation can compromise these organs' detoxification capacity, leading to functional impairment and disease progression. Recent advances in nanotechnology have opened new avenues for enhancing detoxification strategies, particularly through the application of functionalized nanoparticles (NPs). Engineered NPs can selectively bind, sequester, or neutralize harmful compounds, while nano-adsorbents have shown promise in improving the efficiency of renal replacement therapies such as dialysis. Moreover, targeted nanocarriers enable site-specific drug delivery, minimizing off-target effects and enhancing therapeutic efficacy. This review explores the mechanistic interactions of NPs within hepatic and renal detoxification pathways, emphasizing their potential in managing hepatotoxicity and enhancing renal filtration. Highlighted case studies underscore the translational promise of NP-based interventions. Nevertheless, key challenges remain, including NP-induced immunogenicity, cytotoxicity, bioaccumulation, and regulatory hurdles. Future research should prioritize the optimization of NP biocompatibility, refinement of targeted delivery systems, and long-term safety evaluations. A deeper understanding of the nano-bio interface is crucial for unlocking the full potential of nanotechnology in detoxification therapeutics. Addressing these challenges could usher in a new era of precision medicine for liver and kidney health.

Cisplatin (Cis), a common drug for ovarian cancer therapy, faces limited effectiveness due to drug resistance. Citrinin (CTN), a mycotoxin known to induce oxidative stress, has been proposed as a potential sensitizing agent to enhance cisplatin's efficacy. This study investigates the effects of CTN on cisplatin-induced cytotoxicity in SKOV3 ovarian cancer cells, examining its mechanisms through redox imbalance, mitochondrial dysfunction, and cytokine-mediated apoptosis. SKOV3 cells were treated with CTN, cisplatin, and their combination. Various parameters were evaluated, including cell viability, DNA damage, oxidative stress (by measuring ROS, MDA, and antioxidant enzymes like SOD, GSH, and CAT), mitochondrial function (via MMP analysis), and levels of inflammatory cytokines (TNF-α, IL-1β, and NF-κB). Apoptosis was also confirmed with the TUNEL assay. The results showed that the combination of CTN and cisplatin significantly increased cytotoxicity and led to a marked reduction in cell viability. This synergistic effect was confirmed by a significant increase in DNA damage and apoptosis. Mechanistically, the combined treatment led to severe redox imbalance, mitochondrial dysfunction, and increased levels of pro-inflammatory cytokines, all of which contributed to the induction of apoptosis. In conclusion, citrinin enhances cisplatin-induced apoptosis in SKOV3 cancer cells by targeting key pathways, including oxidative stress, mitochondrial dysfunction, and the activation of inflammatory responses. These findings suggest that citrinin.

Senecio brasiliensis is a toxic plant from the Asteraceae family, known to contain bioactive compounds with pharmacological and toxicological potential. This study aimed to investigate the toxicity of Senecio brasiliensis essential oil with in silico and in vivo approaches, using Drosophila melanogaster as the experimental model. The plant was collected, identified and the essential oil extracted from leaves and flowers using hydrodistillation with a Clevenger apparatus. Phytochemical analysis was performed using Gas Chromatography-Mass Spectrometry (GC-MS). Negative geotaxis assay and acetylcholinesterase activity were conducted at 24, 48 and 72 h, along with 144 h survival rate assessment, using different concentrations of the essential oil (3, 30 and 300 μg/mL). Molecular docking analysis was also conducted to assess interactions between the major constituents of the oil with acetylcholinesterase and D. melanogaster cholinergic receptors. Phytochemical analysis resulted in 100% identification of the oil's constituents, notably, bicyclogermacrene (23.36%) and germacrene-D (21.58%) were the major constituents. There was a trend of increased locomotion and a lower acetylcholinesterase activity with 30 and 300 μg/mL of the essential oil. There was also a significant decrease in the 144 h survival rate of the 3 μg/mL group. In silico analysis revealed interactions of major constituents with acetylcholinesterase and both muscarinic and nicotinic receptors. Particularly in B chain of muscarinic receptors, with binding energies of -6.7 kcal/moL for bicyclogermacrene and - 7.6 kcal/mol for germacrene-D. These results may provide insights into the biological effects of the Senecio brasiliensis essential oil and its potential as a bioactive compound.

Many industries are based on chromium, leading to an increase in its environmental residue percentage, especially hexavalent chromium, which increases the risk for several types of cancers and is recognized as a neurotoxicant. Olive oil is a major component of the Mediterranean diet because of its high antioxidant and anti-inflammatory effects. The present study aimed to investigate the adverse effects of hexavalent chromium intoxication (2 mg/b.wt) on several neurophysiological parameters in the cortex and cerebellum and to demonstrate the ameliorating effects of 200 mg/b.wt olive extract on the resulting chromium effect via biochemical, histopathological, and immunohistochemical investigations. The animals were grouped into four groups (control, chromium (Cr), olive extract (OE) and Cr + OE). The results revealed that chromium hexavalent significantly increased the levels of three monoamines, norepinephrine (NE), dopamine (DA), serotonin (5-HT) and both sodium and calcium ions, in addition to increasing the levels of oxidative stress biomarkers, interleukin-1β (IL-1β), interferon (INF-γ), malondialdehyde and nitric oxide. Additionally, chromium caused a significant decrease in potassium ion and glutathione (GSH) levels. Additionally, chromium administration caused intensive necrosis with shrinking in the neural cell while olive extract could mitigate this effect. The coadministration of chromium and olive extract had an ameliorating effect on all the tested parameters. Finally, the ameliorative effect of olive extract may be attributed to its high antioxidant activity and ability to scavenge free radicals.